Glycosidase-Inhibiting Glycomimetic Alkaloids: Biological Activities and Therapeutic Perspectives

摘要

Alkaloids mimicking the structures of sugars inhibit glycosidases because of a structural resemblance to the sugar moiety of the natural substrate. Glycosidases are involved in a wide range of important biological processes, such as intestinal digestion, post-translational processing of glycoproteins and the lysosomal catabolism of glycoconjugates. The realization that alkaloidal glycomimetics might haveenormous therapeutic potential in many diseases such as viral infection, cancer and diabetes led to increasing interest and demand for these compounds. The usefulness of alkaloidal glycomimetics might not be restricted to the inhibition of glycosidases since a number of different competitive inhibitors, all known ot stabilize proteins in their native conformation, are effective in rescuing the processing defect of the mutant enzyme protein. These compounds, which we all "chemical chaperones", also may prove to be effective in correcting a number of other protein folding abnormalities in human genetic diseases.